Department of Environmental Health, Faculty of Pharmaceutical Sciences, Toho University, Funabashi 274-8510, Japan.
Department of Environmental Health, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda 278-8510, Japan.
Int J Mol Sci. 2020 May 24;21(10):3698. doi: 10.3390/ijms21103698.
Syndecan-4 is a member of the syndecan family of transmembrane heparan sulfate proteoglycans, and is involved in cell protection, proliferation, and the blood coagulation-fibrinolytic system in vascular endothelial cells. Heparan sulfate chains enable fibroblast growth factor-2 (FGF-2) to form a complex with its receptor and to transduce the cell growth signal. In the present study, bovine aortic endothelial cells were cultured, and the intracellular signal pathways that mediate the regulation of syndecan-4 expression in dense and sparse cultures by FGF-2 were analyzed. We demonstrated the cell density-dependent differential regulation of syndecan-4 expression. Specifically, we found that FGF-2 upregulated the synthesis of syndecan-4 in vascular endothelial cells via the MEK1/2-ERK1/2 pathway in dense cell cultures, with only a transcriptional induction of syndecan-4 at a low cell density via the Akt pathway. This study highlights a critical mechanism underlying the regulation of endothelial cell functions by proteoglycans.
硫酸乙酰肝素蛋白聚糖-4 是硫酸乙酰肝素蛋白聚糖家族的成员之一，存在于血管内皮细胞的细胞保护、增殖和血液凝固-纤维蛋白溶解系统中。硫酸乙酰肝素链使成纤维细胞生长因子-2（FGF-2）与其受体形成复合物，并传递细胞生长信号。在本研究中，培养牛主动脉内皮细胞，并分析 FGF-2 调节密集和稀疏培养中硫酸乙酰肝素蛋白聚糖-4 表达的细胞内信号通路。我们证明了硫酸乙酰肝素蛋白聚糖-4 表达的细胞密度依赖性差异调节。具体来说，我们发现 FGF-2 通过 MEK1/2-ERK1/2 通路在上皮细胞中上调硫酸乙酰肝素蛋白聚糖-4 的合成，而在低密度细胞中仅通过 Akt 通路诱导硫酸乙酰肝素蛋白聚糖-4 的转录诱导。本研究强调了蛋白聚糖调节内皮细胞功能的关键机制。
